Project Summary The Radiobiology and Imaging Program has been continuously approved by the NCI Cancer Center Support Grant since 1987. The Program seeks to improve patient outcomes through the advanced understanding of how ionizing and non-ionizing radiation interacts with cancer and normal tissues. The Programmatic goals are to: (1) Study molecular mechanisms of radiation response and identify targets to improve radiotherapy. (2) Elucidate mechanisms underlying use of Photodynamic Therapy (PDT) and translate to the clinic. (3) Develop methods for measuring and altering tumor oxygenation and metabolic status; understand the molecular events governing cell death by IR and physiological stresses. (4) Develop novel techniques to image the interaction between radiation, PDT and tissues. (5) Understand the biological effects of protons to inform their effective clinical use. The Program was rated as ?Exceptional? at the time of the 2010 CCSG renewal application and is led by Constantinos Koumenis, PhD, Professor and Director of the Research Division of Radiation Oncology and Amit Maity, MD, PhD, Professor of Radiation Oncology. Drs. Maity and Koumenis are NCI-funded researchers who bring their scientific vision to this Program, which is focused on basic and translational research and the development of investigator-initiated trials. Since the last renewal, the Co- Leaders have recruited new junior and senior scientists, enhanced collaborative peer-reviewed funding and increased the number of investigator-initiated clinical trials involving radiotherapy and imaging. Moreover, Drs. Koumenis and Maity have steered the Program towards new areas of emphasis including combined radiation and immunotherapy modalities and precision medicine and they have expanded the incorporation of imaging modalities into basic and translational efforts. Through this process, they increased interactions with the Immunobiology, Cancer Therapeutics, Breast Cancer and Cancer Control Programs. A major development has been the substantial expansion of both translational and clinical studies of proton therapy. Program members represent six departments from four schools at Penn. During the past five years, translational research has continued to be a major focus. The 33 Program members have $7.7M in research grant funding (annual direct costs), of which $7.5M is peer-reviewed and $3.7M is NCI-funded. There were a total of 405 cancer-related publications authored by Program members during the project period. Of these, 19% are intra- Programmatic, 28% are inter-Programmatic and 53% are multi-institutional.